The DMArepair protein Rad23 can bind multiubiquitinated proteins and the proteasome. Biochemical studies suggested that Rad23functions as a shuttle-factor that can bind and deliver ubiquitinated substrates to the proteasome, and suggested that it might promote protein degradation following DNA damage. Rad23 performs two distinct roles in nucleotide excision-repair (NER). One function involves interaction with the DNA repair protein Rad4. Remarkably,this interaction prevents Rad4 degradation by the Ub/proteasome pathway. A second function involves Rad23 interaction with the proteasome, but this function is not related to Rad4-stabilization, although it is required for NER. There is compelling evidence that Rad23/proteasome interaction is required for all its diverse functions, including (NER). However, previous studies were based on a deletion mutant that lacked the UbL domain, which binds the proteasome. Since the UbL domain has other physiological partners, these studies did not characterize the specific defect of the mutant protein. A sequence in Rad23 that binds and stabilizes Rad4 (R4B) was identified. As expected, removal of this sequence prevented interaction with Rad4, and caused UV sensitivity. Surprisingly, loss of R4B also abolished Rad23 interaction with multiubiquitinated proteins. Studies are proposed to characterize the UbL and R4B motifs, by generating well-defined mutations. These studies will be important for further testing the hypothesis that Rad23 is a shuttle-factor. Despite extensive characterization of NER proteins, a function for Rad4 has not been described. Our studies suggest that Rad4 might influence Rad23 function, and studies are proposed to investigate this idea. The loss of Rad23 and the proteasome subunit RpnIO caused severe growth and proteolytic defects. STS1 was isolated as genetic suppressor of these defects. Preliminary studies indicate that Sts1 might facilitate the proper sub-cellular distribution of proteasomes, and might specifically regulate nucleo- cytoplasmic transport. An important objective of this study is to determine how Sts1 suppressed the defects of the rac/23 rpnlO mutant. Since Rad23 and proteasomes are localized to the nucleus in response to DNA damage, these studies can improve our understanding of the function of Rad23 in protein degradation and DNA repair. Multiubiquitin chains were believed to be sufficient for targeting substrates to the proteasome. However, emerging evidence suggest that the translocation of ubiquitinated proteins to the proteasome requires regulatory factors, such as Rad23. We discovered that Rad23 binds the proteasome, and similar findings have now been described for other UbL-UBA proteins, from yeast to human. Our studies will advance our understanding of the mechanism of substrate delivery to the proteasome, and Rad23 function in NER.